Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy

Palma, Luigi de; Marinelli, Massimiliano; Pavan, Matteo; Orazi, Alessandro

doi:10.1016/j.jbspin.2007.04.019

Cited by 46 publications

(39 citation statements)

References 28 publications

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“…MAFbx has been recognized as a critical regulator of muscle atrophy (Palma et al, 2008). Therefore, inhibition of MAFbx could be one of the approaches to clinically intervene in various conditions associated with muscle atrophy.…”

Section: Discussionmentioning

confidence: 99%

“…MAFbx works coordinately with proteasomes and degrades a series of proteins during muscle atrophy (Palma et al, 2008). Low expression levels of MAFbx may limit protein breakdown in muscle wasting and lead to the regeneration of muscle fibers.…”

Section: Inhibition Of Mafbx Expression Reactivates Myogenic Differenmentioning

confidence: 99%

“…Studies have shown that these two proteins are induced dramatically during almost every kind of atrophy and play a critical role in mediating the loss of muscle protein (Gomes et al, 2001;Attaix et al, 2005). MAFbx is induced 8-to 40-fold in muscle atrophy during fasting, diabetes, cancer, and renal failure; up to 3-fold in hind limb suspension, immobilization, and denervation; and 10-fold in cachexia or dexamethasone administration models (Lecker et al, 2004;Palma et al, 2008). Mice lacking MAFbx developed normal muscle but showed a significant attenuation of muscle atrophy (Bodine et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Atrogin-1/MAFbx Expression by Adenovirus-Delivered Small Hairpin RNAs Attenuates Muscle Atrophy in Fasting Mice

et al. 2011

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Atrogin-1 or muscle atrophy F-box (MAFbx) is a major atrophy-related E3 ubiquitin ligase highly expressed in skeletal muscle during muscle atrophy and other disease states such as sepsis, cancer cachexia, and fasting. In this paper, we report experiments inhibiting MAFbx activity in fasting mice and in the skeletal myoblast cell line C2C12 via an adenovirus-mediated small hairpin RNA (shRNA) expression system in order to assess its suitability as a therapeutic target. Our results demonstrated that downregulation of MAFbx by shRNAs attenuated muscle loss induced by fasting in mice. Furthermore, we showed that when MAFbx expression was blocked both in cells and in fasting mice, the level of a myogenic factor, MyoD, was upregulated; whereas a muscle negative regulator, growth differentiation factor (GDF)-8 (myostatin), was suppressed. Our results also suggested that lower levels of MAFbx could also enhance muscle cell differentiation that corresponded to the reduced expression of GDF-8 and the increased level of MyoD. Taken together, the present study showed that MAFbx could be a potential molecular target for treating muscle atrophy.

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Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of Mafbx Expression Reactivates Myogenic Differenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Atrogin-1/MAFbx Expression by Adenovirus-Delivered Small Hairpin RNAs Attenuates Muscle Atrophy in Fasting Mice

et al. 2011

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“…However, the role of the E3 ligases in human cachexia is less well defined. Studies that included patients following bed rest, limb amputation for vascular disease, limb immobilisation, chronic obstructive pulmonary disease, amyotrophic lateral sclerosis and ageing demonstrate both increased and decreased expression of MuRF1 and MAFBx [30][31][32][33] but evidence for an increase in human cancer cachexia is lacking [34]. There are also data that suggest dissociation between protein dynamics in vivo and activation of UPP signalling in human skeletal muscle [35].…”

Section: Proteolytic Pathwaysmentioning

confidence: 99%

Muscle protein kinetics in cancer cachexia

Johns

Stephens

Preston

2012

Current Opinion in Supportive &Amp; Palliative Care

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Only by having an appreciation of the complex regulation of muscle protein synthesis and degradation, will potential new therapeutics be able to be developed. This review identifies known targets in molecular pathways of current interest, explores methods used to find novel genes which may be involved in muscle kinetics and also highlights ways in which muscle kinetics may be measured to assess the efficacy of such interventions.

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“…Two of these FBXO genes have been directly implicated in degenerative disorders: FBXO7, also known as PARK15, has been linked to a severe early onset form of PD known as Parkinson-Pyramidal syndrome (Di Fonzo et al, 2009), while FBXO32, or atrogin, has been linked to muscle wasting phenotypes (de Palma et al, 2008). Both FBXO7 and FBXO32 belong to the same evolutionary sub-family along with another gene, FBXO9, which has not been well-characterized (Cenciarelli et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Altered expression of CG5961, a putative Drosophila melanogaster homologue of FBXO9, provides a new model of Parkinson disease

Merzetti

Staveley

2016

Genet. Mol. Res.

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ABSTRACT. F-box proteins act as the protein recognition component of the Skp-Cul-F-box class of ubiquitin ligases. Two members of a gene sub-family encoding these proteins, FBXO7 and FBXO32, have been implicated in the onset and progression of degenerative disease. FBXO7 is responsible for rare genetic forms of Parkinson disease, while FBXO32 has been implicated in muscle wasting. The third gene in this family, FBXO9, is related to growth signaling, but the role of this gene in degenerative disease pathways has not been thoroughly investigated. Characterizing the putative Drosophila melanogaster homologue of this gene, CG5961, enables modeling and analysis of the consequence of targeted alteration of gene function and the effects on the overall health of the organism. or CG5961-RNAi in the dopaminergic neurons led to a reduced lifespan compared to that in lacZ controls. We showed that protein structures of CG5961 and FBXO9 are highly similar and studied the effects of altered expression of CG5961 in neuron-rich tissues. Our results suggest that CG5961 activity is necessary for the proper formation of neuronal tissue and that targeted alteration of gene expression in dopaminergic neurons leads to a reduced lifespan.

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Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy

Cited by 46 publications

References 28 publications

Inhibition of Atrogin-1/MAFbx Expression by Adenovirus-Delivered Small Hairpin RNAs Attenuates Muscle Atrophy in Fasting Mice

Inhibition of Atrogin-1/MAFbx Expression by Adenovirus-Delivered Small Hairpin RNAs Attenuates Muscle Atrophy in Fasting Mice

Muscle protein kinetics in cancer cachexia

Altered expression of CG5961, a putative Drosophila melanogaster homologue of FBXO9, provides a new model of Parkinson disease

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